Aspartame is potentially harmful to the developing fetus, despite wide acclaim for use as an artificial sweetener. This proposal intends to investigate evidence of mental retardation and/or developmental disabilities due to ingesting aspartame during normal gestation. Structural and functional brain development will be quantified and general somatic development will be evaluated in the offspring of guinea pigs who consume aspartame during pregnancy. Since brain development is in utero in the guinea pig and man, the results of this investigation will be applicable to human development. Treatment: Aspartame will be administered to pregnant guinea pigs via drinking water throughout the entire period of gestation. Since phenylalanine has been shown to be responsible for most of the toxic effects of aspartame and animals metabolize phenylalanine more rapidly than humans, additional phenylalanine will be given to some treatment groups. The treatment groups are: 1). Control (water); 2). 34mg/kg/day aspartame; 3). 34 mg/kg/day aspartame with phenylalanine; 4). 1000 mg/kg/day aspartame; 5). 1000 mg/kg/day aspartame with phenylalanine. Analyses: Ten offspring (5 males and 5 females) in each of five groups will be studied. Litter data will be collected and one pup/litter sacrificed on the day of birth for blood analysis (liver and kidney function tests), soft tissue inspection, and brain removal for morphometrics. Brain metabolism will be quantified in newborn and adult offspring using the deoxyglucose method to see if the systems within the brain, including the neuroendocrine axis, function normally. The offspring will be extensively evaluated for reflexes, reactivity, activity, perseveration, and visual discrimination. This basic research will evaluate the teratogenicity of moderate and toxic doses of aspartame consumed in increasingly greater quantities by pregnant women. Since the blood levels of phenylalanine will be monitored in this experiment, the results will be applicable to human gestation. The results will also be particularly important to women with hepatic insufficiency and homozygous and heterozygous phenylketonurics (PKU) because of thei rinability to metabolize phenylalanine. Consumption of even moderate quantities of aspartame during pregnancy by members of these populations may produce a dramatic increase in the number of children born with diminished brain function.